Objective assessment of PTSD severity via smartphone-based ocular biomarkers

Abstract Background Post-traumatic stress disorder (PTSD) is a prevalent psychiatric condition, yet no current assessment approach, whether clinician interview or self-report, incorporates objective physiological measurement. The absence of a validated biomarker is a fundamental gap. Methods We evaluated smartphone-based pupillometry (Senseye Diagnostic Tool, iPhone) in 38 trauma-exposed veterans in an intensive outpatient program. Pupil-to-iris ratio (PIR) was measured during pupillary light reflex (PLR) and affective image viewing (AIV) tasks across treatment and follow-up visits (96 PLR, 88 AIV sessions; same-day PCL-5, BDI-II, BAI). Continuous, hierarchical, and within-person mixed-effects regressions isolated PTSD-specific variance and tested within-person symptom tracking. Results Constriction PIR correlated with PCL-5 severity (R2 = 0.109, p = 0.001), concentrated in avoidance (R2 = 0.171) and negative alterations in cognitions/mood (R2 = 0.224, both p < 0.001) rather than arousal. After adjusting for demographics and comorbidity, PTSD clusters explained an additional 16.4% of variance (p < 0.001), about seven times the comorbid contribution. Dark Mean PIR was elevated in PTSD + sessions (p = 0.019). Within-person, participants' own PCL-5 changes tracked concurrent changes in Dark Mean PIR (β = 0.0024, p = 0.006) and Constriction PIR (β = 0.0014, p = 0.031), independent of BDI-II and BAI. AIV trended similarly but was not significant. Conclusions Smartphone pupillometry shows promise as an objective, physiologically grounded approach to PTSD assessment. These proof-of-concept findings show that the biomarker captures PTSD-specific variance independent of comorbid psychopathology and tracks within-person symptom change. Validation in larger, more diverse samples is required to establish clinical utility.